Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in children and young adults with chronic kidney disease (CKD). The applicant's long-term career goal is to define biologic targets for interventions to prevent and slow progression of CVD in children with CKD through advancing Patient-Oriented Research (POR). Since early years of his career, the applicant's research has been focusing on elucidating the mechanisms of cardiovascular abnormalities in children with CKD through epidemiological and translational studies. He has maintained continuous funding at the federal level in this area of research. He currently has an R01 examining the role of adiponectin and other adipokines in the development of cardiovascular abnormalities in children with CKD. Dr. Mitsnefes is also a Co-investigator and a Co-Chair of the Cardiovascular Committee for the NIH funded CKiD study (U01 mechanism), a multicenter effort designed to study children with CKD. The aim of this K24 program is to provide the candidate protected time and resources to build a comprehensive program to study CVD in children with CKD. Specific aims of this award are: 1) further the candidate's own research and 2) mentor junior faculty and fellows who are pursuing POR in pediatric nephrology. The first aim will be based and build upon candidate's previous research and will examine early biological markers of myocardial dysfunction in children on maintenance dialysis and after kidney transplantation: 1) left ventricular myocardial circumferential strain (Ecc), and 2) muscle energy metabolism by 31Phosphorus Magnetic Resonance Spectroscopy (31P MRS), and 3) left atrial size and markers of diastolic function. The second aim is based upon applicant's previous mentoring experience: since 2003 Dr. Mitsnefes has mentored 8 research fellows, and has been senior author on 17 peer-reviewed articles with his mentee as the first author. The Mentoring Plan for early career faculty and research fellows will incorporate the existing T32, K12 and K30 training programs at Cincinnati Children's Hospital Medical Center to produce outstanding clinical scientists who go on to be independent investigators. It will consist of: 1) individualized mentoring of 2 junior faculty who are planning to apply for K23 awards; 2) intensive practical training in patient-oriented research within the context of the current research projects of candidate's R01 for 2 fellows as well as development of their own independent research projects (F32 award); 3) course work in fulfillment of Master's of Science degree in the Graduate Program in Clinical and Translational Research at the University of Cincinnati; 4) participation of fellows in established other didactic programs on manuscript and grant writing, design of clinical trials and clinical research methodology, and ethics in clinical research. Cincinnati Children's Hospital Medical Center provides an ideal setting for this award because of the commitment to POR and ongoing initiatives to promote innovative clinical research through the presence of a strong Center for Clinical and Translational Science and Training. PUBLIC HEALTH RELEVANCE: Cardiovascular disease (CVD) is the major cause of death in children and young adults with chronic kidney disease (CKD). the mechanisms of cardiovascular disease (CVD) in children with chronic kidney disease (CKD). The aim of this K24 program is to provide the candidate protected time and resources to build a comprehensive program to better understand the mechanisms of heart problems in children on dialysis and with kidney transplant. This goal will be achieved by expansion of candidate's own research through using MRI technology to study early heart abnormalities, and by mentoring young investigators who are interested in studying heart problems in children with CKD. By understanding the cause of heart abnormalities, we hope to develop the program for prevention or treatment of this problem in children with CKD.